Figure 2.

Steps of MPXV entry into host cells [13,14,59–62]. (1) Schematic of the structure of MPXV. (2) Both the EEV and IMV virions penetrate the host membrane by binding and macropinocytosis. MPXV virions use glycosaminoglycans as host receptors. (3) After the internal virion components enter the cytoplasm, core uncoating occurs and this process leads to delivery of the MPXV genome and accessory proteins to the cytosol. (4) The released MPXV genome is used as a template for DNA replication. (5) Early viral DNA transcription followed by translation into the host ribosome occurs to encode essential proteins. Early proteins aid in DNA replication. (6) These proteins interact with host sensor proteins resulting in internal and external modulations. The major intracellular modulations include prevention of viral genome detection, induction of cell cycle arrest, apoptosis inhibition, inhibition of the antiviral system and modulation of some host cellular signalling pathways. Early proteins play essential extracellular roles as immunomodulatory agents and as growth factor-like domains that stimulate onset of mitosis in neighbouring cells. (7) Early proteins are used in production of intermediate proteins. (8) These proteins are involved in late transcription and translation processes and aid in DNA replication. (9) Late proteins are essential components for viral assembly. (10) Viral morphogenesis occurs by formation of inner tubular nucleocapsid structure folding and assembly of viral glycoproteins to generate MV virions. (11) Except those released via infected cell lysis, MV virions transit to the Golgi apparatus along microtubules for double membrane wrapping. (12) The resulting EEV virions exit the infected cell by two routes: by the actin tail assembly, which provides enough force to propel the virions out of the cell or by budding from a cellular membrane (Created with BioRender.com).